Yue Jian, Fang Huiying, Yang Qian, Feng Rui, Ren Guosheng
Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Breast Surgery, Gaozhou People's Hospital, Gaozhou, Guangdong, China.
Front Oncol. 2025 Mar 26;15:1565090. doi: 10.3389/fonc.2025.1565090. eCollection 2025.
The metabolism of amino acids and derivatives (MAAD) is closely related to the occurrence and development of colorectal cancer (CRC), but the specific regulatory mechanisms are not yet clear. This study aims to explore the role of MAAD in the progression of colorectal cancer and ultimately identify key molecules that may become potential therapeutic targets for CRC.
This study integrates bulk transcriptome and single-cell transcriptome to analyze and identify key MAAD-related genes from multiple levels. Subsequently, numerous machine learning methods were incorporated to construct MAAD-related prognostic models, and the infiltration of immune cells, tumor heterogeneity, tumor mutation burden, and potential pathway changes under different modes were analyzed. Finally, key molecules were identified for experimental validation.
We successfully constructed prognostic models and Nomograms based on key MAAD-related molecules. There was a notable survival benefit observed for low-risk patients when contrasted with their high-risk counterparts. In addition, the high-risk group had a poorer response to immunotherapy and stronger tumor heterogeneity compared with the low-risk group. Further research found that by knocking down the MAAD-related gene. LSM8, the malignant characteristics of colorectal cancer cell lines were significantly alleviated, suggesting that LSM8 may become a potential therapeutic target.
The MAAD-related gene LSM8 is likely involved in the progression of CRC and could be a hopeful target for therapeutic intervention.
氨基酸及其衍生物代谢（MAAD）与结直肠癌（CRC）的发生发展密切相关，但其具体调控机制尚不清楚。本研究旨在探讨MAAD在结直肠癌进展中的作用，并最终确定可能成为CRC潜在治疗靶点的关键分子。
本研究整合批量转录组和单细胞转录组，从多个层面分析和鉴定与MAAD相关的关键基因。随后，采用多种机器学习方法构建与MAAD相关的预后模型，并分析不同模式下免疫细胞浸润、肿瘤异质性、肿瘤突变负担及潜在通路变化。最后，鉴定关键分子进行实验验证。
我们成功构建了基于关键MAAD相关分子的预后模型和列线图。与高风险患者相比，低风险患者有显著的生存获益。此外，与低风险组相比，高风险组对免疫治疗的反应较差，肿瘤异质性更强。进一步研究发现，敲低与MAAD相关的基因LSM8后，结直肠癌细胞系的恶性特征明显减轻，提示LSM8可能成为潜在的治疗靶点。
与MAAD相关的基因LSM8可能参与CRC的进展，有望成为治疗干预的靶点。
